1642-49-5Relevant academic research and scientific papers
Synthesis and Properties of Aromatic-Terminated Diacetylene Organogelators and Their Application to Photopatterning of Polydiacetylenes
Aoki, Ken'Ichi,Horitsugu, Kousuke,Narazaki, Kenta,Seki, Atsushi,Takahashi, Daiki,Tamaoki, Nobuyuki
, p. 13160 - 13169 (2021/11/16)
A series of simply structured diacetylene-diamide-based gelators (DAGs) with aromatic terminals were synthesized, and their gelation and subsequent photopolymerization abilities were analyzed. DAGs with an adequate spacer length (n) and tolyl terminals (DA-Tn) interacted with aromatic solvents, such as benzene and xylenes, at elevated temperatures. During the subsequent cooling process, the DAGs interacted with each other through CH-πinteractions at their terminal positions. They also formed one-dimensional hydrogen bonding arrays through secondary amides, leading to stable organogels. These gels polymerized into π-conjugated polydiacetylenes (PDAs) under ultraviolet irradiation. In the p-xylene gels of DA-Tn, the spacer length exerted characteristic odd-even effects on the photopolymerization rates over a certain range (n = 3-6), which can be explained by periodic changes in the uniformity of the molecular packing modes. When the gelling solvent was changed to cyclohexane, the gelation and photopolymerization abilities were greatly improved because the DA-Tn gel networks became highly crystallized and transparent to ultraviolet light (254 nm). The ultimate conversion to PDA from DA-T8/cyclohexane gels was 45.2 wt %. Applying photolithographic techniques to the DAG with excellent photopolymerizability in the film state, we successfully fabricated microscale photopatterns of PDA. We also established a convenient removal process (development process) of DA monomers in unexposed areas. The resulting PDA patterns were quite stable to ambient light stimuli.
DIMERIC IMMUNO-MODULATORY COMPOUNDS AGAINST CEREBLON-BASED MECHANISMS
-
Page/Page column 144-145, (2020/02/06)
Disclosed are small molecules against cereblon to enhance effector T cell function. Methods of making these molecules and methods of using them to treat various disease states are also disclosed.
INSULIN CONJUGATES
-
Paragraph 0580; 0592-0595, (2020/07/05)
The present invention relates to a conjugate comprising a sulfonamide of formula (I) and an active pharmaceutical ingredient such as an insulin analog comprising at least one mutation relative to the parent insulin, wherein the insulin analog comprises a mutation at position B16 which is substituted with a hydrophobic amino acid and/or a mutation at position B25 which is substituted with a hydrophobic amino acid. The present invention further relates to a sulfonamide of formula (A). Moreover, the present invention relates to an insulin analog comprising at least one mutation relative to the parent insulin.
Synergistic Gold and Copper Dual Catalysis for Intramolecular Glaser–Hay Coupling: Rapid Total Synthesis of Ivorenolide B
Rangaraju, Sudheer K.,Gonela, Uma Maheshwar,Kavita, Aala,Yadav, Jhillu S.,Mohapatra, Debendra K.
supporting information, p. 4376 - 4380 (2018/09/11)
A synergistic dual catalysis approach involving gold and copper catalysts for the synthesis of macrolactones bearing 1,3-butadiynes through an intramolecular Glaser–Hay coupling reaction in good yield is described. This dual catalytic system exhibited good selectivity, reactivity and functional group tolerance. This unique process offers a paradigm shift: the potential as well as the versatility of this novel method is not only exemplified for the synthesis of macrolactones of different ring size but also for the rapid total synthesis of ivorenolide B, a new class of macrolides endowed with conjugated 1,3-diyne motif, having impressive immunosuppressive activities.
Succinct synthesis of saturated hydroxy fatty acids and: In vitro evaluation of all hydroxylauric acids on FFA1, FFA4 and GPR84
Kaspersen, Mads Holmgaard,Jenkins, Laura,Dunlop, Julia,Milligan, Graeme,Ulven, Trond
, p. 1360 - 1365 (2017/07/07)
Saturated hydroxy fatty acids make up a class of underexplored lipids with potentially interesting biological activities. We report a succinct and general synthetic route to saturated hydroxy fatty acids hydroxylated at position 6 or higher, and exemplify this with the synthesis of hydroxylauric acids. All regioisomers of hydroxylauric acids were tested on free fatty acid receptors FFA1, FFA4 and GPR84. The results show that the introduction of a hydroxy group and its position have a high impact on receptor activity.
Configurational Assignment of ‘Cryptochiral’ 10-Hydroxystearic Acid Through an Asymmetric Catalytic Synthesis
Brunner, Andreas,Hintermann, Lukas
, p. 928 - 943 (2016/12/09)
An asymmetric catalytic total synthesis of (S)-10-hydroxystearic acid (1) for comparison of its absolute configuration to that of samples obtained by fermentative hydration of oleic acid is reported. The synthesis involves two catalytic key-steps, namely Ru-catalyzed anti-Markovnikov hydration of 9-decynoic acid (7) to 10-oxodecanoic acid (5), followed by titanium-mediated asymmetric catalytic addition of dioctylzinc (25) to 5 in presence of the chiral ligand N,N’-((1R,2R)-cyclohexane-1,2-diyl)bis(1,1,1-trifluoromethanesulfonamide) (6). The synthesis is short and efficient and avoids use of protecting groups. Ozonolysis of 10-undecynoic acid (9) to 5 provides an alternative entry point into the synthetic route. The double dehydrobromination of (ω,ω-1)-dibromoalkanoic acids to ω-alkynoic acids under a variety of conditions was investigated with 10,11-dibromoundecanoic acid (11) as model substrate and using qNMR to quantify all reaction products. The synthetic approaches presented here have the potential to be generalized to the asymmetric catalytic synthesis of a variety of n-hydroxy-fatty acids.
Methods and compositions for protein labeling using lipoic acid ligases
-
Page/Page column 35; 36, (2016/04/05)
The present disclosure provides compositions and methods of use thereof for labeling peptide and proteins in vitro or in vivo. The methods described herein employ lipoic acid ligase or mutants thereof, and lipoic acid analogs (e.g., lipoic acid analogs comprising a resorufin moiety) recognized by lipoic acid ligase and lipoic acid ligase mutants. Also provided herein is a method of imaging protein-protein interaction via a reaction mediated by lipoic acid ligase.
Design and synthesis of protein kinase C epsilon selective diacylglycerol lactones (DAG-lactones)
Ann, Jihyae,Yoon, Suyoung,Baek, Jisoo,Kim, Da Hye,Lewin, Nancy E.,Hill, Colin S.,Blumberg, Peter M.,Lee, Jeewoo
, p. 332 - 341 (2015/05/04)
DAG-lactones afford a synthetically accessible, high affinity platform for probing structure activity relationships at the C1 regulatory domain of protein kinase C (PKC). Given the central role of PKC isoforms in cellular signaling, along with their differential biological activities, a critical objective is the design of isoform selective ligands. Here, we report the synthesis of a series of DAG-lactones varying in their side chains, with a particular focus on linoleic acid derivatives. We evaluated their selectivity for PKC epsilon versus PKC alpha both under standard lipid conditions (100% phosphatidylserine, PS) as well as in the presence of a nuclear membrane mimetic lipid mixture (NML). We find that selectivity for PKC epsilon versus PKC alpha tended to be enhanced in the presence of the nuclear membrane mimetic lipid mixture and, for our lead compound, report a selectivity of 32-fold.
The first stereoselective synthesis of a dithiane derivative of the C18 β-diketodiene system proposed for an active compound isolated from Cantharellus cibarius (chanterelle)
Grodner, Jacek,Golebiewski, W. Marek,Willis, Michael C.,Osborne, James D.,Gucma, Miros?aw
, p. 1181 - 1189 (2015/04/14)
A stereocontrolled synthesis of a thioketal system that is a direct precursor of an active compound isolated from chanterelle was accomplished by using readily available methyl 11-[2-(2-oxoethyl)-1,3-dithian-2-yl]undec-9-ynoate as a key intermediate. The synthesis involves simple and straightforward reactions, such as addition of a lithiated alkyne to an aldehyde, alkyne hydrogenation using nickel boride, alcohol oxidation with Dess-Martin periodinane, and Z-to-E enone isomerization.
Identification of a novel NAMPT inhibitor by combinatorial click chemistry and chemical refinement
Theeramunkong,Galli,Grolla,Caldarelli,Travelli,Massarotti,Troiani,Alisi,Orsomando,Genazzani,Tron
, p. 1891 - 1897 (2015/10/20)
The identification of compounds able to inhibit the NAD salvage pathway is experiencing a growing popularity as it has been proposed to be a novel target for antitumoral and anti-inflammatory drugs. In this manuscript, we used the copper-catalyzed [3+2] cycloaddition between azides and alkynes (click chemistry) to identify novel NAMPT inhibitors with a triazole-containing tail group. 720 compounds were synthesized in the first round, allowing the identification of 17 hit compounds. The second round of optimization brought about the discovery of compound 43 which displayed a cytotoxicity of 20 nM on neuroblastoma cancer cells and an inhibition of NAMPT of 114 nM.
